Use of GLP-1 receptor agonist in preparation of drug for treating or preventing pet diseases

Abstract

Provided is use of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating or preventing pet diseases. The GLP-1 receptor agonist is semaglutide. The GLP-1 receptor agonist has significant effects in weight reduction and blood glucose lowering of cats and dogs, and has fewer side effects. The side effects include, but are not limited to: gastrointestinal reactions and cardiac safety risks.

Description

Use of GLP-1 receptor agonists in the manufacture of a medicament for treating or preventing a disease in a pet TECHNICAL FIELD

[0001] The present application belongs to the field of animal therapeutics, and specifically relates to use of GLP-1 receptor agonists in the manufacture of a medicament for treating or preventing a disease in a pet. BACKGROUND

[0002] With the development of social economy, more and more residents start to raise pets, and raising pets has become an indispensable part of their lives. The number of pets in China is increasing rapidly, especially the number of dogs and cats, which has led to a rapid increase in demand for pet products and animal products.

[0003] There are very few pet-specific drugs in China. As of 2017, there were only 187 pet-specific drugs approved by the Ministry of Agriculture, including 180 pet-specific chemical drugs and 7 pet-specific biological drugs. Although the "Veterinary Drug Administration Regulations" has prohibited the use of human drugs in pets, due to the lack of pet-specific drugs, pet owners in China still use human drugs, and some human drugs are not effective in pets. Therefore, various problems related to animal clinics and hospitals continue to arise, and the most prominent problem is the misuse of human drugs by animal clinics and hospitals. The result of mixing human and animal drugs can cause serious harm. Due to the differences in physiological mechanisms and metabolic characteristics between humans and animals, and the large differences in drug tolerance among different species of animals, some human drugs may be ineffective or may not fully exert their efficacy when used in animals, and some may have unexpected side effects, even leading to the death of pets. For example, the use of antibacterial drugs in animals can easily lead to the emergence of drug-resistant bacteria, which can cause immeasurable risks and losses to public health.

[0004] Obesity is a common problem in pets. Obesity disrupts a pet's metabolism, increasing the risk of diabetes, cardiovascular disease, joint problems, skin diseases, and other serious health issues. Currently, for canine weight loss treatment, Slentrol (deltastatin) and Yarvitan (mitatastatin) are approved for marketing. Yarvitan is the first weight loss drug specifically developed for dogs, achieving a weight loss of approximately 6.4 kg per month. Both Slentrol and Yarvitan are selective microsomal triglyceride transfer protein (MTP) inhibitors, acting on intestinal epithelial cells to prevent lipid absorption and have a local effect on satiety. Both products have varying degrees of adverse reactions. Yarvitan's product information states that it is contraindicated in dogs with impaired liver function, dogs allergic to the active ingredient or any excipients, pregnant and lactating dogs, dogs under 18 months of age, and dogs whose overweight or obesity is caused by accompanying systemic diseases such as hypothyroidism or hyperadrenocorticism. Slentrol's product information states that it is contraindicated in dogs during their growth period, pregnant or lactating dogs, dogs with impaired liver function, dogs allergic to the active ingredient or excipients, dogs whose overweight or obesity is caused by accompanying systemic diseases (such as hypothyroidism or hyperadrenocorticism), and cats due to the risk of hepatic steatosis. To date, no weight-loss drugs for cats have been approved.

[0005] Diabetes is also a common endocrine disease in pets (such as cats and dogs). Current medications for pet diabetes include insulin products and sodium-glucose cotransporter 2 (SGLT2) inhibitors. Insulin products are mostly used to treat pet diabetes, such as porcine insulin zinc suspension (…). Intervet (Netherlands); Vetsulin (Merck), protamine zinc recombinant human insulin ( Boehringer Ingelheim (IGI) recommends appropriate insulin administration based on its onset and duration of action. However, improper long-term injection techniques can easily cause subcutaneous fat nodules, leading to reduced glucose-lowering efficacy. Bexaglitazone (Bexaglitazone) is an approved SGLT2 inhibitor. TM American Reliance Blue and Veragragliflozin (Boehringer Ingelheim), but these two products cannot be used in cats that have previously been treated with insulin, and the main adverse reaction, ketoacidosis, can easily lead to death if not corrected in time.

[0006] Somatuline has been proven to have good efficacy in reducing weight and lowering blood sugar in humans; in the discovery and preclinical stage of human somatuline, many animal models (such as mice, rats, monkeys, dogs or pigs) are used for pharmacokinetic studies. However, there is no specific study on somatuline for pets, especially for pet cats to reduce weight and lower blood sugar. It is well known that it is difficult to predict the drug response of animals without specific testing of animals. Therefore, the effect of somatuline on weight loss and blood sugar lowering in pets still needs to be confirmed.

[0007] In summary, it is crucial to find a long-acting, less adverse pet weight loss and blood sugar lowering drug. SUMMARY

[0008] One object of the present disclosure is to provide the use of a GLP-1 receptor agonist in the preparation of a pet medicine. The GLP-1 receptor agonist of the present invention is somatuline. The GLP-1 receptor agonist of the present invention has excellent GLP-1 activity in various species of animals, such as non-primate and non-rodent animals, including but not limited to dogs, cats. The GLP-1 receptor agonist of the present disclosure has a significant effect on weight loss and blood sugar lowering in cats and dogs compared with the blank control group. The GLP-1 receptor agonist of the present invention has lower side effects, including but not limited to gastrointestinal reactions and cardiac safety risks.

[0009] One object of the present invention is to provide the use of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating or preventing a disease in a pet, the GLP-1 receptor agonist being selected from any one of the compounds in WO2006097537, preferably somatuline.

[0010] Another object of the present invention is to provide a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof for preventing or treating a disease in a pet, the GLP-1 receptor agonist being selected from any one of the compounds in WO2006097537, preferably somatuline.

[0011] Another object of the present invention is to provide a method for preventing or treating a disease in a pet, the method comprising administering to an animal in need thereof a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof, the GLP-1 receptor agonist being selected from any one of the compounds in WO2006097537, preferably somatuline.

[0012] Another object of the present invention is to provide a method for reducing food intake in a pet, the method comprising administering to a pet in need thereof a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof, the GLP-1 receptor agonist being selected from any one of the compounds in WO 2006097537, preferably somatuline.

[0013] The present invention also provides a method for increasing the duration of action of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof in pets, characterized in that the GLP-1 receptor agonist used is selected from any compound in WO2006097537, preferably semaglutide. One embodiment provides the use of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any of the above embodiments in the preparation of a medicament for treating or preventing diseases in pets, said diseases being hyperglycemia, impaired glucose tolerance, diabetes (including type I and type II diabetes), obesity, hypertension, dyslipidemia, cognitive impairment, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular diseases, stroke, inflammatory bowel syndrome, indigestion and gastric ulcers and related complications.

[0014] One embodiment provides the use of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of the above embodiments, said GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the prevention, delay or treatment of type II diabetes in pets.

[0015] One embodiment provides the use of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of the above embodiments for the preparation of a medicament for reducing pet food intake, reducing β-cell apoptosis, increasing β-cell function and β-cell quantity and / or restoring β-cell glucose sensitivity.

[0016] In one embodiment, the present invention provides a method for preventing or treating type II diabetes in pets, comprising administering to the animal in need an effective amount of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof.

[0017] In one embodiment, the present invention provides a method for improving glycemic control in pets with type 2 diabetes, comprising administering an effective amount of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof to the pet in need as an adjunct to diet and exercise.

[0018] In one embodiment, the present invention provides a method for long-term weight management in overweight or obese pets, comprising administering an effective amount of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof to the pet in need as an adjunct to a low-calorie diet and increased physical activity.

[0019] In one embodiment, the present invention provides a method for treating metabolic syndrome, comprising administering an effective amount of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof to a pet in need.

[0020] In another embodiment, the present invention provides a method for preventing or treating dyslipidemia, obesity, and / or hepatic steatosis in pets associated with insulin resistance and diabetes, comprising administering to the pet in need an effective amount of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof.

[0021] In addition, the present invention provides a method for preventing or treating weakness in pets or increasing bone strength in said animals, comprising administering an effective amount of semaglutide or a pharmaceutically acceptable salt thereof to the pet in need.

[0022] In another embodiment, the present invention provides a method for treating osteopenia and bone / joint diseases in pets, such as knee osteoarthritis, hip osteoarthritis, degenerative spondylitis, and low back pain, comprising administering to the pet in need an effective amount of the semaglutide described herein or a pharmaceutically acceptable salt thereof.

[0023] In one embodiment, the present invention provides the GLP-1 receptor agonist of the present invention or a pharmaceutically acceptable salt thereof as an adjunct to diet and exercise for glycemic control in pets with type II diabetes.

[0024] In one embodiment, the present invention provides the GLP-1 receptor agonist of the present invention or a pharmaceutically acceptable salt thereof as an adjunct to a low-calorie diet and increased physical activity in overweight or obese pets for long-term weight management.

[0025] One embodiment provides the use according to any one of the above embodiments for the preparation of a medicament for the treatment or prevention of the aforementioned diseases in dogs or cats.

[0026] The above-described activation of GLP-1 receptors by the compounds of this invention suggests that the GLP-1 receptor agonist of this invention or a pharmaceutically acceptable salt thereof can be used as a medicine for the prevention or treatment of the following diseases: for example, symptomatic obesity, obesity based on simple obesity, disease states or diseases associated with obesity, eating disorders, diabetes (e.g., type 1 diabetes, type 2 diabetes, gestational diabetes, obesity-related diabetes), hyperlipidemia (e.g., hypertriglyceridemia, hypercholesterolemia, high LDL-cholesterol, low HDL-cholesterol, postprandial hyperlipidemia), hypertension, heart failure, complications of diabetes (e.g., neuropathy, nephropathy, retinopathy, diabetic cardiomyopathy, cataracts, megavascular disease, osteoporosis, hyperosmolar diabetic coma), diabetic gangrene, xerostomia, hearing loss, cerebrovascular disease, peripheral circulatory disorders, metabolic syndrome (having three or more disease states selected from hypertriglyceridemia, low HDL-cholesterol, hypertension, abdominal obesity, and impaired glucose tolerance), and / or sarcopenia, etc.

[0027] Examples of symptomatic obesity include: endocrine obesity (e.g., Cushing's syndrome, hypothyroidism, insulinoma, obesity-related type II diabetes, pseudohypoparathyroidism, hypogonadism), central obesity (e.g., hypothalamic obesity, frontal lobe syndrome, Klein-Lewin syndrome), hereditary obesity (e.g., Prader-Willi syndrome, Laureus-Müller-Bissau syndrome), drug-induced obesity (e.g., steroid, phenothiazine, insulin, sulfonylurea drugs, beta-blocker-induced obesity), and so on.

[0028] Examples of disease states or conditions associated with obesity include: glucose intolerance, diabetes (especially type II diabetes, obesity-related diabetes), lipid metabolism disorders (synonymous with hyperlipidemia), hypertension, heart failure, hyperuricemia, fatty liver (including non-alcoholic hepatitis), coronary artery disease (myocardial infarction, angina pectoris), cerebral infarction (cerebral thrombosis, transient ischemic attack), bone / joint diseases (knee osteoarthritis, hip osteoarthritis, degenerative spondylitis, low back pain), sleep apnea syndrome / Pickwick syndrome, menstrual disorders (abnormal menstrual cycles, amenorrhea, abnormal menstrual symptoms), metabolic syndrome, etc.

[0029] According to the present invention, GLP-1 receptor agonists can react with any of a variety of inorganic and organic acids to form pharmaceutically acceptable acid addition salts. Pharmaceutically acceptable salts and common methods for preparing them are well known in the art.

[0030] In one embodiment, the GLP-1 receptor agonist is administered in a formulation. In addition to the GLP-1 receptor agonist described herein, the formulation may contain pharmaceutically acceptable carriers, diluents, fillers, disintegrants, binders, lubricants, surfactants, hydrophobic mediators, water-soluble mediators, emulsifiers, buffers, humectants, solubilizers, and preservatives. The formulations described herein may be in the following forms: solutions, suspensions, emulsions, tablets, pills, granules, capsules, liquid-containing capsules, powders, sustained-release formulations, suppositories, aerosols, sprays, or any other suitable form. Saline solutions and aqueous solutions of glucose and glycerol may be used as liquid carriers, particularly for injectable solutions.

[0031] According to the present invention, GLP-1 receptor agonists can be administered in any conventional manner via any route in which they are active, such as systemic or local administration. For example, they can be administered by inhalation, by storage injection or by implantation, and can be administered via, but not limited to, parenteral, subcutaneous, intravenous, intramuscular, intraperitoneal, percutaneous, oral, oral, sublingual or ocular routes.

[0032] According to the present invention, a GLP-1 receptor agonist can be used in combination therapy with at least one other therapeutic agent. In some embodiments, the GLP-1 receptor agonist can be administered in combination with other diabetes medications, weight-loss medications, blood pressure medications, and / or cholesterol medications. The GLP-1 receptor agonist can act in combination or synergistically with other therapeutic agents. The other therapeutic agents can be included in the same composition as the GLP-1 receptor agonist or can be included in separate compositions. The composition containing the GLP-1 receptor agonist can be administered simultaneously or sequentially with another therapeutic agent. In another embodiment, the composition containing the GLP-1 receptor agonist of the present invention is administered before or after administration of other therapeutic agents.

[0033] In a preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises a pharmaceutical formulation of at least one semaglutide and propylene glycol, wherein the propylene glycol is present in the formulation at a final concentration of about 1 mg / mL to about 100 mg / mL, and wherein the formulation has a pH of about 7.0 to about 10.0; preferably, the concentration of propylene glycol is about 1 mg / mL to about 50 mg / mL, for example about 1 mg / mL to about 25 mg / mL, or even more preferably about 1 mg / mL to about 16 mg / mL; the pH of the formulation is about 7.0 to about 9.5, for example about 7.0 to about 8.3, or even more preferably about 7.3 to about 8.3; the formulation further comprises a preservative, the concentration of which is further preferably 0.1 mg / mL to about 20 mg / mL; the formulation further comprises a buffer, the buffer being further preferably selected from glycylglycine, L-histidine, Hepes, N-glycine, and disodium phosphate dihydrate.

[0034] In a preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises a liquid pharmaceutical composition of semaglutide and not more than 0.01% (w / w) phenol, wherein the composition a) is an aqueous solution containing at least 60% w / w water; or b) further comprises one or more pharmaceutically acceptable excipients selected from buffers or isotonic agents; preferably, the composition does not contain phenol; and / or, the composition is an aqueous solution containing at least 60% w / w water; and / or, the concentration of the semaglutide is 0.5-10 mg / mL or 0.01-5 mg / mL of the composition; and / or, the composition comprises one or more pharmaceutically acceptable excipients, more preferably, the excipients are selected from buffers or isotonic agents; and / or, the composition does not contain preservatives; and / or, the pH of the composition is in the range of 6.0-10.0, such as pH 7.0-7.8.

[0035] In a preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises semaglutide, not more than 0.1% (w / w) of phenol, and more than 6.4 mg / mL of sodium chloride, and optionally further comprises histidine; preferably, the formulation does not contain phenol; and / or, the formulation is substantially composed of: a) semaglutide, optionally b) not more than 0.1% (w / w) of phenol, c) more than 6.4 mg / mL of sodium chloride, d) a buffer, e) at least 60% (w / w) of water, optionally f) histidine, and optionally g) one or more agents for adjusting pH, such as HCl, NaOH, or acetic acid / acetate; more preferably, the formulation comprises 0.5-10 mg / mL of semaglutide and 8.1 mg / mL of sodium chloride. -12 mg / mL sodium chloride; for example, 8.2-8.9 mg / mL sodium chloride; 0.5-3.5 mg / mL semaglutide, for example 3.2 mg / mL semaglutide; and / or, comprising histidine; and / or, the liquid pharmaceutical composition further comprising a buffer, for example, the buffer being present at a concentration of 0.01-50 mM, or, for example, the buffer being a phosphate buffer, and the concentration of the phosphate buffer optionally being 1-2 mg / mL; and / or, the pH of the liquid pharmaceutical composition being in the range of 6.0-10.0, such as 7-8; for example, comprising 0.5-3.5 mg / mL semaglutide, 8.25 mg / mL sodium chloride, and 1.42 mg / mL disodium hydrogen phosphate dihydrate.

[0036] In a preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises:

[0037] -Semaglutide;

[0038] -The concentration of the semaglutide is greater than 15 mM and less than or equal to 45 mM, such as 16-45 mM, such as 20-45 mM, such as 20-40 mM, such as 25-45 mM, such as 25-40 mM, such as 20-35 mM, such as 20-30 mM, such as 25-35 mM, such as about 30 mM of phosphate;

[0039] -90-99% w / w of water; and

[0040] - pH is 7.0-8.0, for example, about 7.4;

[0041] Preferably, it comprises:

[0042] - Semaglutide at a concentration of 0.1-10 mg / mL;

[0043] - Concentrations greater than 15 mM and less than or equal to 45 mM, such as 16-45 mM, 20-45 mM, 20-40 mM, 25-45 mM, 25-40 mM, 20-35 mM, 20-30 mM, 25-35 mM, such as approximately 30 mM phosphate; and

[0044] - pH is 7-8, for example, about 7.4;

[0045] The formulation optionally contains histidine; and / or

[0046] It further contains a tensile agent, such as propylene glycol, potassium chloride and / or sodium chloride;

[0047] The semaglutide formulation described above is used in injection devices.

[0048] In a preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises a solid composition for oral administration, comprising semaglutide and N-(8-(2-hydroxybenzoyl)amino)octanoate, wherein the amount of semaglutide is 5 to 20 mg, the N-(8-(2-hydroxybenzoyl)amino)octanoate is sodium N-(8-(2-hydroxybenzoyl)amino)octanoate (SNAC), and the amount of SNAC is 300 mg; the composition is in tablet form; for example, the amount of semaglutide is 5 to 15 mg, or, for example, 5 mg, 10 mg, 15 mg, or 20 mg; preferably, the composition comprises at least one other pharmaceutically acceptable excipient; the weight of the tablet is further preferably 175-1000 mg; for example, 200-800 mg. 00 mg; or, for example, 400 mg, 600 mg, or 800 mg; and / or, the excipient is selected from one or more of binders, fillers, disintegrants, lubricants, and flow aids; preferably, the composition contains 0.1-10% w / w of a binder, such as 0.2-4% w / w or 0.5-3% w / w, or, for example, 1% w / w or 2% w / w of a binder; more preferably, the binder is povidone; and / or, the composition contains 5-40% w / w of a filler, such as 10-30% w / w or 5-25% w / w; or, for example, the composition contains 10.9% w / w, 18% w / w, 19.5% w / w, or 20.5% w / w of a filler; the filler is more preferably microcrystalline cellulose; most preferably avicel. pH 102 or avicel pH 200; and / or, the composition contains 0.1-10% w / w or 0.5-5% w / w of a lubricant or flow aid, for example, the composition contains 1-3.5% w / w or 1% w / w of a lubricant or flow aid; and / or, the excipient is magnesium stearate; which further preferably contains 0.1-10% w / w of a binder, 5-40% w / w of a filler, and 0.1-10% w / w of a lubricant or flow aid.

[0049] In a preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises a solid composition for oral administration, comprising semaglutide and N-(8-(2-hydroxybenzoyl)amino)octanoate, wherein the amount of semaglutide is 4 to 20 mg, the N-(8-(2-hydroxybenzoyl)amino)octanoate is sodium N-(8-(2-hydroxybenzoyl)amino)octanoate (SNAC), and the amount of SNAC is 100 mg; the composition is in tablet form.

[0050] In a further preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises 0.5 mg / mL semaglutide, 1.42 mg / mL disodium hydrogen phosphate dihydrate, 8.25 mg / mL sodium chloride, and water, with a pH of approximately 7.4, said pH being adjustable with hydrochloric acid or sodium hydroxide.

[0051] In a further preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises 1 mg / mL semaglutide, 1.42 mg / mL disodium hydrogen phosphate dihydrate, 8.25 mg / mL sodium chloride, and water, with a pH of approximately 7.4, said pH being adjustable with hydrochloric acid or sodium hydroxide.

[0052] In a further preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises 2 mg / mL semaglutide, 1.42 mg / mL disodium hydrogen phosphate dihydrate, 8.25 mg / mL sodium chloride, and water, with a pH of approximately 7.4, said pH being adjustable with hydrochloric acid or sodium hydroxide.

[0053] In a further preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises 2.27 mg / mL semaglutide, 1.42 mg / mL disodium hydrogen phosphate dihydrate, 8.25 mg / mL sodium chloride, and water, with a pH of approximately 7.4, said pH being adjustable with hydrochloric acid or sodium hydroxide.

[0054] In a further preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises 3.2 mg / mL semaglutide, 1.42 mg / mL disodium hydrogen phosphate dihydrate, 8.25 mg / mL sodium chloride, and water, with a pH of approximately 7.4, said pH being adjustable with hydrochloric acid or sodium hydroxide.

[0055] In a further preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises 0.68 mg / mL semaglutide, 1.42 mg / mL disodium hydrogen phosphate dihydrate, 1.40 mg / mL propylene glycol, 5.50 mg / mL phenol, and water, with a pH of approximately 7.4, said pH being adjustable with hydrochloric acid or sodium hydroxide.

[0056] In a further preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises 1.34 mg / mL semaglutide, 1.42 mg / mL disodium hydrogen phosphate dihydrate, 1.40 mg / mL propylene glycol, 5.50 mg / mL phenol, and water, with a pH of approximately 7.4, said pH being adjustable with hydrochloric acid or sodium hydroxide.

[0057] In a further preferred embodiment, the GLP-1 receptor agonist formulation of the present invention comprises 2.68 mg / mL semaglutide, 1.42 mg / mL disodium hydrogen phosphate dihydrate, 1.40 mg / mL propylene glycol, 5.50 mg / mL phenol, and water, with a pH of approximately 7.4, said pH being adjustable with hydrochloric acid or sodium hydroxide.

[0058] In a further preferred embodiment, the GLP-1 receptor agonist formulation of the present invention is selected from the trade names OZEMPIC, WEGOVY, or RYBELSUS. Preferably, the GLP-1 receptor agonist formulation is selected from any of the following strengths of OZEMPIC: 0.68 mg / mL, 3 mL; 1.34 mg / mL, 1.5 mL; 1.34 mg / mL, 3 mL; or 2.68 mg / mL, 3 mL; or the GLP-1 receptor agonist formulation is selected from any of the following strengths of WEGOVY: 0.68 mg / mL, 1.5 mL; 1.34 mg / mL, 1.5 mL; 1.34 mg / mL, 3 mL; 2.27 mg / mL, 3 mL; or 3.2 mg / mL, 3 mL; or the GLP-1 receptor agonist formulation is selected from any of the following strengths of RYBELSUS: 1.5 mg; 4 mg; 9 mg; 25 mg; 3 mg; 7 mg; or 14 mg.

[0059] In some embodiments, the GLP-1 receptor agonist of the present invention or a formulation thereof is used to prepare a drug for treating pet-related diseases, preferably a dog or a cat, more preferably a cat, such as a domestic shorthair cat or a blue cat, or even a domestic shorthair cat.

[0060] In some embodiments, the GLP-1 receptor agonist of the present invention or a formulation thereof is used to treat type II diabetes, overweight and / or obesity in cats; in a preferred embodiment, the GLP-1 receptor agonist of the present invention or a formulation thereof is used to treat obesity in cats, wherein the cat obesity is characterized by a (BCS) ≥ 6, for example, the cat obesity is characterized by a (BCS) ≥ 6.6 and / or a weight > 4.5 kg, or for example, ≥ 4.8 kg, or for example, ≥ 4.8 kg and ≤ 5.1 kg; preferably, the cat is older than 8 months.

[0061] In some embodiments, the GLP-1 receptor agonist of the present invention or a formulation thereof is administered in the form of a solution or suspension.

[0062] In some implementations, the GLP-1 receptor agonist or its formulation described herein is administered via subcutaneous injection.

[0063] In some embodiments, the dosage regimen of the GLP-1 receptor agonist or its formulation described herein in cats is 0.2-1.6 mg / kg QW, preferably 0.79 mg / kg QW.

[0064] In some embodiments, the GLP-1 receptor agonist or its formulation described herein is administered to cats once a week, preferably for a period of 5 weeks.

[0065] In some preferred embodiments, the GLP-1 receptor agonist or its formulation described herein is administered to cats once weekly at doses of 0.24 mg / kg QW, 0.24 mg / kg QW, 0.79 mg / kg QW, 0.79 mg / kg QW, and 0.79 mg / kg QW for a duration of 5 weeks.

[0066] In some embodiments, the GLP-1 receptor agonist of the present invention or a formulation thereof is used to treat type II diabetes, overweight and / or obesity in dogs; in a preferred embodiment, the GLP-1 receptor agonist of the present invention or a formulation thereof is used to treat obesity in dogs, wherein the dog obesity is characterized by (BCS) ≥ 6, for example, the dog obesity is characterized by (BCS) ≥ 6 and / or weight > 15 kg; preferably, the dog is over 1 year old.

[0067] In some embodiments, the dosage regimen of the GLP-1 receptor agonist or its formulation described herein in dogs is 0.04-0.4 mg / kg QW, preferably 0.047 mg / kg QW, 0.079 mg / kg QW, 0.4 mg / kg QW, or a combination thereof.

[0068] In some embodiments, the GLP-1 receptor agonist or its formulation described herein is administered to dogs once weekly, preferably for a period of 6 weeks.

[0069] In some preferred embodiments, the GLP-1 receptor agonist or its formulation described herein is administered to dogs once weekly at doses of 0.047 mg / kg QW, 0.047 mg / kg QW, 0.079 mg / kg QW, 0.4 mg / kg QW, 0.4 mg / kg QW, and 0.4 mg / kg QW for a duration of 6 weeks. Detailed Implementation

[0070] 1. Use of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment or prevention of a disease or disease state in a pet, wherein the GLP-1 receptor agonist is semaglutide;

[0071] The diseases mentioned include hyperglycemia, impaired glucose tolerance, diabetes (including type 1 and type 2 diabetes), obesity, hypertension, dyslipidemia, cognitive impairment, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular diseases, stroke, inflammatory bowel syndrome, indigestion and gastric ulcers and related complications;

[0072] And / or, the compound or a pharmaceutically acceptable salt thereof is used to prepare a drug for reducing animal food intake, reducing β-cell apoptosis, increasing β-cell function and β-cell quantity and / or restoring β-cell glucose sensitivity;

[0073] And / or, the diseases mentioned include metabolic disorders, dyslipidemia associated with insulin resistance and diabetes, obesity and / or hepatic steatosis;

[0074] And / or, the diseases mentioned include osteopenia, bone / joint diseases such as knee osteoarthritis, hip osteoarthritis, and / or degenerative spondylitis;

[0075] And / or, the compound or a pharmaceutically acceptable salt thereof may be used in overweight or obese animals as an adjunct to a low-calorie diet and increased physical activity for long-term weight management.

[0076] And / or, the disease is overweight, symptomatic obesity, obesity based on simple obesity, a disease state or disease associated with obesity, eating disorder, diabetes (e.g., type 1 diabetes, type 2 diabetes, gestational diabetes, obesity-related diabetes), hyperlipidemia (e.g., hypertriglyceridemia, hypercholesterolemia, high LDL-cholesterol, low HDL-cholesterol, postprandial hyperlipidemia), hypertension, heart failure, complications of diabetes (e.g., neuropathy, nephropathy, retinopathy, diabetic cardiomyopathy, cataracts, megavascular disease, osteoporosis, hyperosmolar diabetic coma), diabetic gangrene, xerostomia, hearing loss, cerebrovascular disease, peripheral circulatory disorder, metabolic syndrome (having three or more disease states selected from hypertriglyceridemia, low HDL-cholesterol, hypertension, abdominal obesity, and impaired glucose tolerance), and / or sarcopenia.

[0077] 2. The use according to embodiment 1, characterized in that the symptomatic obesity includes: endocrine obesity (e.g., Cushing's syndrome, hypothyroidism, insulinoma, obesity-related type II diabetes, pseudohypoparathyroidism, hypogonadism), central obesity (e.g., hypothalamic obesity, frontal lobe syndrome, Klein-Lewin syndrome), hereditary obesity (e.g., Prader-Willi syndrome, Laureus-Müller-Bissau syndrome), and drug-induced obesity (e.g., obesity induced by steroids, phenothiazines, insulin, sulfonylureas, or beta-blockers).

[0078] 3. According to the use described in Implementation Scheme 1, the obesity-related disease states or diseases include: glucose intolerance, diabetes (especially type II diabetes, obesity-related diabetes), lipid metabolism disorders (synonymous with the above-mentioned hyperlipidemia), hypertension, heart failure, hyperuricemia, fatty liver (including non-alcoholic hepatitis), coronary heart disease (myocardial infarction, angina pectoris), cerebral infarction (cerebral thrombosis, transient ischemic attack), bone / joint diseases (knee osteoarthritis, hip osteoarthritis, degenerative spondylitis, low back pain), sleep apnea syndrome / Pickwick syndrome, menstrual disorders (abnormal menstrual cycle, amenorrhea, abnormal menstrual symptoms), and metabolic syndrome.

[0079] 4. The use according to any one of embodiments 1-3, characterized in that the GLP-1 receptor agonist is administered in formulation form.

[0080] 5. The use according to embodiment 4, characterized in that the formulation of the GLP-1 receptor agonist is administered in the form of a solution or suspension.

[0081] 6. The use according to embodiment 5, characterized in that the formulation of the GLP-1 receptor agonist is administered by subcutaneous injection.

[0082] 7. The use according to any one of embodiments 5-6, characterized in that the formulation of the GLP-1 receptor agonist preferably comprises, as in any of the following embodiments:

[0083] Option 1: Semaglutide 0.5 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0084] Option 2: Semaglutide 1 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, with a pH of approximately 7.4. The pH can be adjusted with hydrochloric acid or sodium hydroxide.

[0085] Option 3: Semaglutide 2 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, with a pH of approximately 7.4. The pH can be adjusted with hydrochloric acid or sodium hydroxide.

[0086] Option 4: Semaglutide 2.27 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0087] Option 5: Semaglutide 3.2 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0088] Option 6: Semaglutide 0.68 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0089] Option 7: Semaglutide 1.34 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0090] Option 8: Semaglutide 2.68 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH approximately 7.4. The pH can be adjusted with hydrochloric acid or sodium hydroxide.

[0091] Based on the total volume of the formulation.

[0092] 8. The use according to any one of embodiments 1-7, characterized in that the pet is a dog or a cat, preferably a cat, such as a Chinese domestic cat or a blue cat, or for example, a Chinese domestic cat.

[0093] 9. The use according to any one of embodiments 1-8, characterized in that the GLP-1 receptor agonist or its formulation is used to treat type II diabetes, overweight and / or obesity in cats; preferably, the GLP-1 receptor agonist or its formulation is used to treat overweight and / or obesity in cats; more preferably, the overweight and / or obesity in cats is characterized by a (BCS) ≥ 6, for example, the overweight and / or obesity in cats is characterized by a (BCS) ≥ 6.6 and / or a weight > 4.5 kg, or for example, ≥ 4.8 kg, or even for example, ≥ 4.8 kg and ≤ 5.1 kg; even more preferably, the age of the cat is 8 months or older.

[0094] 10. The use according to any one of embodiments 1-9, characterized in that the dosage regimen of the GLP-1 receptor agonist or its formulation in cats is 0.2-1.6 mg / kg QW, preferably, the dosage regimen of the GLP-1 receptor agonist or its formulation in cats is 0.24 mg / kg QW, 0.79 mg / kg QW, or a combination thereof; preferably, the dosage regimen of the GLP-1 receptor agonist or its formulation in cats is 0.79 mg / kg QW.

[0095] 11. The use according to any one of embodiments 1-10, characterized in that the GLP-1 receptor agonist or its formulation is administered to cats once a week, preferably for a period of 5 weeks.

[0096] 12. The use according to embodiment 11, characterized in that the dosing regimen of the GLP-1 receptor agonist or its formulation is 0.24 mg / kg QW, 0.24 mg / kg QW, 0.79 mg / kg QW, 0.79 mg / kg QW, 0.79 mg / kg QW.

[0097] 13. The use according to any one of the embodiments 1-7, characterized in that the pet is a dog or a cat, preferably a dog.

[0098] 14. The use according to any one of embodiments 1-7 and 13, characterized in that the GLP-1 receptor agonist or its formulation is used to treat type II diabetes, overweight and / or obesity in dogs; in a preferred embodiment, the GLP-1 receptor agonist or its formulation of the present invention is used to treat obesity in dogs, wherein the canine obesity is characterized by (BCS) ≥ 6, for example, the canine obesity is characterized by (BCS) ≥ 6 and / or weight > 15 kg; preferably, the dog is over 1 year old.

[0099] 15. The use according to any one of embodiments 1-7 and 13-14, characterized in that the dosage regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.04-0.4 mg / kg, preferably, the dosage regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.047 mg / kg, 0.079 mg / kg, 0.4 mg / kg or a combination thereof.

[0100] 16. The use according to any one of embodiments 1-7 and 13-15, characterized in that the GLP-1 receptor agonist or its formulation is administered to dogs once a week, preferably for a period of 6 weeks.

[0101] 17. The use according to any one of embodiments 1-7 and 13-16, characterized in that the dosing regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.047 mg / kg QW, 0.047 mg / kg QW, 0.079 mg / kg QW, 0.4 mg / kg QW, 0.4 mg / kg QW or 0.4 mg / kg QW.

[0102] 18. A GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof for the prevention or treatment of diseases in pets, wherein the GLP-1 receptor agonist is semaglutide; the diseases include hyperglycemia, impaired glucose tolerance, diabetes (including type I and type II diabetes), obesity, hypertension, dyslipidemia, cognitive impairment, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular diseases, stroke, inflammatory bowel syndrome, indigestion and gastric ulcers and related complications;

[0103] And / or, the compound or a pharmaceutically acceptable salt thereof is used to prepare a drug for reducing animal food intake, reducing β-cell apoptosis, increasing β-cell function and β-cell quantity and / or restoring β-cell glucose sensitivity;

[0104] And / or, the diseases mentioned include metabolic disorders, dyslipidemia associated with insulin resistance and diabetes, obesity and / or hepatic steatosis;

[0105] And / or, the diseases mentioned include osteopenia, bone / joint diseases such as knee osteoarthritis, hip osteoarthritis, and / or degenerative spondylitis;

[0106] And / or, the compound or a pharmaceutically acceptable salt thereof may be used in overweight or obese animals as an adjunct to a low-calorie diet and increased physical activity for long-term weight management.

[0107] And / or, the disease is overweight, symptomatic obesity, obesity based on simple obesity, a disease state or disease associated with obesity, eating disorder, diabetes (e.g., type 1 diabetes, type 2 diabetes, gestational diabetes, obesity-related diabetes), hyperlipidemia (e.g., hypertriglyceridemia, hypercholesterolemia, high LDL-cholesterol, low HDL-cholesterol, postprandial hyperlipidemia), hypertension, heart failure, complications of diabetes (e.g., neuropathy, nephropathy, retinopathy, diabetic cardiomyopathy, cataracts, megavascular disease, osteoporosis, hyperosmolar diabetic coma), diabetic gangrene, xerostomia, hearing loss, cerebrovascular disease, peripheral circulatory disorder, metabolic syndrome (having three or more disease states selected from hypertriglyceridemia, low HDL-cholesterol, hypertension, abdominal obesity, and impaired glucose tolerance), and / or sarcopenia.

[0108] 19. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to embodiment 18, characterized in that the symptomatic obesity includes: endocrine obesity (e.g., Cushing's syndrome, hypothyroidism, insulinoma, obesity-related type II diabetes, pseudohypoparathyroidism, hypogonadism), central obesity (e.g., hypothalamic obesity, frontal lobe syndrome, Klein-Lewin syndrome), hereditary obesity (e.g., Prader-Willi syndrome, Laureus-Müller-Bissau syndrome), and drug-induced obesity (e.g., steroid, phenothiazine, insulin, sulfonylurea drugs, β-blocker-induced obesity).

[0109] 20. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to embodiment 18, characterized in that the obesity-related disease state or disease includes: glucose intolerance, diabetes (especially type II diabetes, obese diabetes), lipid metabolism disorders (synonymous with hyperlipidemia above), hypertension, heart failure, hyperuricemia, fatty liver (including non-alcoholic hepatitis), coronary heart disease (myocardial infarction, angina pectoris), cerebral infarction (cerebral thrombosis, transient ischemic attack), bone / joint diseases (knee osteoarthritis, hip osteoarthritis, degenerative spondylitis, low back pain), sleep apnea syndrome / Pickwick syndrome, menstrual disorders (abnormal menstrual cycle, amenorrhea, abnormal menstrual symptoms), and metabolic syndrome.

[0110] 21. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 18-20, characterized in that the GLP-1 receptor agonist is administered in formulation form.

[0111] 22. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to embodiment 21, characterized in that the formulation of the GLP-1 receptor agonist is administered in the form of a solution or suspension.

[0112] 23. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to embodiment 22, characterized in that the formulation of the GLP-1 receptor agonist is administered by subcutaneous injection.

[0113] 24. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 22-23, characterized in that the formulation of the GLP-1 receptor agonist preferably comprises, as in any of the following embodiments:

[0114] Option 1: Semaglutide 0.5 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0115] Option 2: Semaglutide 1 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, with a pH of approximately 7.4. The pH can be adjusted with hydrochloric acid or sodium hydroxide.

[0116] Option 3: Semaglutide 2 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, with a pH of approximately 7.4. The pH can be adjusted with hydrochloric acid or sodium hydroxide.

[0117] Option 4: Semaglutide 2.27 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0118] Option 5: Semaglutide 3.2 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0119] Option 6: Semaglutide 0.68 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0120] Option 7: Semaglutide 1.34 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0121] Option 8: Semaglutide 2.68 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH approximately 7.4. The pH can be adjusted with hydrochloric acid or sodium hydroxide.

[0122] Based on the total volume of the formulation.

[0123] 25. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 18-24, characterized in that the pet is a dog or a cat, preferably a cat, such as a domestic shorthair cat or a blue cat, or, for example, a domestic shorthair cat.

[0124] 26. A GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 18-25, characterized in that the GLP-1 receptor agonist or a formulation thereof is used to treat type II diabetes, overweight and / or obesity in cats; preferably, the GLP-1 receptor agonist or a formulation thereof is used to treat overweight and / or obesity in cats; further preferably, the overweight and / or obesity in cats is characterized by a (BCS) ≥ 6, for example, the overweight and / or obesity in cats is characterized by a (BCS) ≥ 6.6 and / or a weight > 4.5 kg, or for example, ≥ 4.8 kg, or for example, ≥ 4.8 kg and ≤ 5.1 kg; even more preferably, the age of the cat is 8 months or older.

[0125] 27. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 18-26, characterized in that the dosing regimen of the GLP-1 receptor agonist or its formulation in cats is 0.2-1.6 mg / kg QW, preferably, the dosing regimen of the GLP-1 receptor agonist or its formulation in cats is 0.24 mg / kg QW, 0.79 mg / kg QW, or a combination thereof; preferably, the dosing regimen of the GLP-1 receptor agonist or its formulation in cats is 0.79 mg / kg QW.

[0126] 28. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 18-27, characterized in that the GLP-1 receptor agonist or its formulation is administered to cats once a week, preferably for a period of 5 weeks.

[0127] 29. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to embodiment 28, characterized in that the dosing regimen of the GLP-1 receptor agonist or its formulation is 0.24 mg / kg QW, 0.24 mg / kg QW, 0.79 mg / kg QW, 0.79 mg / kg QW, 0.79 mg / kg QW.

[0128] 30. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 18-24, characterized in that the pet is a dog or a cat, preferably a dog.

[0129] 31. A GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 18-24 and 30, characterized in that the GLP-1 receptor agonist or a formulation thereof is used to treat type II diabetes, overweight and / or obesity in dogs; in a preferred embodiment, the GLP-1 receptor agonist or a formulation thereof of the present invention is used to treat obesity in dogs, wherein the canine obesity is characterized by (BCS) ≥ 6, for example, the canine obesity is characterized by (BCS) ≥ 6 and / or weight > 15 kg; preferably, the dog is over 1 year old.

[0130] 32. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 18-24 and 30-31, characterized in that the dosing regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.04-0.4 mg / kg QW, preferably, the dosing regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.047 mg / kg QW, 0.079 mg / kg QW, 0.4 mg / kg QW, or a combination thereof.

[0131] 33. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 18-24 and 30-32, characterized in that the GLP-1 receptor agonist or its formulation is administered to dogs once a week, preferably for a period of 6 weeks.

[0132] 34. The GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof according to any one of embodiments 18-24 and 30-33, characterized in that the dosing regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.047 mg / kg QW, 0.047 mg / kg QW, 0.079 mg / kg QW, 0.4 mg / kg QW, 0.4 mg / kg QW, or 0.4 mg / kg QW.

[0133] 35. A method for preventing or treating a disease in a pet, the method comprising administering to an animal in need a GLP-1 receptor agonist of the present invention or a pharmaceutically acceptable salt thereof, said GLP-1 receptor agonist being semaglutide;

[0134] The diseases mentioned include hyperglycemia, impaired glucose tolerance, diabetes (including type 1 and type 2 diabetes), obesity, hypertension, dyslipidemia, cognitive impairment, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular diseases, stroke, inflammatory bowel syndrome, indigestion and gastric ulcers and related complications;

[0135] And / or, the compound or a pharmaceutically acceptable salt thereof is used to prepare a drug for reducing animal food intake, reducing β-cell apoptosis, increasing β-cell function and β-cell quantity and / or restoring β-cell glucose sensitivity;

[0136] And / or, the diseases mentioned include metabolic disorders, dyslipidemia associated with insulin resistance and diabetes, obesity and / or hepatic steatosis;

[0137] And / or, the diseases mentioned include osteopenia, bone / joint diseases such as knee osteoarthritis, hip osteoarthritis, and / or degenerative spondylitis;

[0138] And / or, the compound or a pharmaceutically acceptable salt thereof may be used in overweight or obese animals as an adjunct to a low-calorie diet and increased physical activity for long-term weight management.

[0139] And / or, the disease is overweight, symptomatic obesity, obesity based on simple obesity, a disease state or disease associated with obesity, eating disorder, diabetes (e.g., type 1 diabetes, type 2 diabetes, gestational diabetes, obesity-related diabetes), hyperlipidemia (e.g., hypertriglyceridemia, hypercholesterolemia, high LDL-cholesterol, low HDL-cholesterol, postprandial hyperlipidemia), hypertension, heart failure, complications of diabetes (e.g., neuropathy, nephropathy, retinopathy, diabetic cardiomyopathy, cataracts, megavascular disease, osteoporosis, hyperosmolar diabetic coma), diabetic gangrene, xerostomia, hearing loss, cerebrovascular disease, peripheral circulatory disorder, metabolic syndrome (having three or more disease states selected from hypertriglyceridemia, low HDL-cholesterol, hypertension, abdominal obesity, and impaired glucose tolerance), and / or sarcopenia.

[0140] 36. The method according to embodiment 35, wherein the symptomatic obesity includes: endocrine obesity (e.g., Cushing's syndrome, hypothyroidism, insulinoma, obesity-related type II diabetes, pseudohypoparathyroidism, hypogonadism), central obesity (e.g., hypothalamic obesity, frontal lobe syndrome, Klein-Lewin syndrome), hereditary obesity (e.g., Prader-Willi syndrome, Laureus-Müller-Bissau syndrome), and drug-induced obesity (e.g., obesity induced by steroids, phenothiazines, insulin, sulfonylureas, or beta-blockers).

[0141] 37. The method according to embodiment 35, characterized in that the obesity-related disease states or diseases include: glucose intolerance, diabetes (especially type II diabetes, obesity-related diabetes), lipid metabolism disorders (synonymous with the above-mentioned hyperlipidemia), hypertension, heart failure, hyperuricemia, fatty liver (including non-alcoholic hepatitis), coronary heart disease (myocardial infarction, angina pectoris), cerebral infarction (cerebral thrombosis, transient ischemic attack), bone / joint diseases (knee osteoarthritis, hip osteoarthritis, degenerative spondylitis, low back pain), sleep apnea syndrome / Pickwick syndrome, menstrual disorders (abnormal menstrual cycle, amenorrhea, abnormal menstrual symptoms), and metabolic syndrome.

[0142] 38. The method according to any one of embodiments 35-37, wherein the GLP-1 receptor agonist is administered in formulation form.

[0143] 39. The method according to embodiment 38, wherein the formulation of the GLP-1 receptor agonist is administered in the form of a solution or suspension.

[0144] 40. The method according to embodiment 39, wherein the formulation of the GLP-1 receptor agonist is administered by subcutaneous injection.

[0145] 41. The method according to any one of embodiments 39-40, characterized in that the formulation of the GLP-1 receptor agonist preferably comprises, as in any of the following embodiments:

[0146] Option 1: Semaglutide 0.5 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0147] Option 2: Semaglutide 1 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, with a pH of approximately 7.4. The pH can be adjusted with hydrochloric acid or sodium hydroxide.

[0148] Option 3: Semaglutide 2 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, with a pH of approximately 7.4. The pH can be adjusted with hydrochloric acid or sodium hydroxide.

[0149] Option 4: Semaglutide 2.27 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0150] Option 5: Semaglutide 3.2 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0151] Option 6: Semaglutide 0.68 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0152] Option 7: Semaglutide 1.34 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide;

[0153] Option 8: Semaglutide 2.68 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH approximately 7.4. The pH can be adjusted with hydrochloric acid or sodium hydroxide.

[0154] Based on the total volume of the formulation.

[0155] 42. The method according to any one of embodiments 35-41, wherein the pet is a dog or a cat, preferably a cat, such as a Chinese domestic cat or a blue cat, or for example, a Chinese domestic cat.

[0156] 43. The method according to any one of embodiments 35-42, characterized in that the GLP-1 receptor agonist or its formulation is used to treat type II diabetes, overweight and / or obesity in cats; preferably, the GLP-1 receptor agonist or its formulation is used to treat overweight and / or obesity in cats; more preferably, the overweight and / or obesity in cats is characterized by a (BCS) ≥ 6, for example, the overweight and / or obesity in cats is characterized by a (BCS) ≥ 6.6 and / or a weight > 4.5 kg, or for example, ≥ 4.8 kg, or even for example, ≥ 4.8 kg and ≤ 5.1 kg; even more preferably, the age of the cat is 8 months or older.

[0157] 44. The method according to any one of embodiments 35-43, characterized in that the dosing regimen of the GLP-1 receptor agonist or its formulation in cats is 0.2-1.6 mg / kg QW, preferably, the dosing regimen of the GLP-1 receptor agonist or its formulation in cats is 0.24 mg / kg QW, 0.79 mg / kg QW, or a combination thereof; preferably, the dosing regimen of the GLP-1 receptor agonist or its formulation in cats is 0.79 mg / kg QW.

[0158] 45. The method according to any one of embodiments 35-44, characterized in that the GLP-1 receptor agonist or its formulation is administered to cats once a week, preferably for a period of 5 weeks.

[0159] 46. ​​The method according to embodiment 45, wherein the dosing regimen of the GLP-1 receptor agonist or its formulation is 0.24 mg / kg QW, 0.24 mg / kg QW, 0.79 mg / kg QW, 0.79 mg / kg QW, or 0.79 mg / kg QW.

[0160] 47. The method according to any one of embodiments 35-41, wherein the pet is a dog or a cat, preferably a dog.

[0161] 48. The method according to any one of embodiments 35-41 and 47, characterized in that the GLP-1 receptor agonist or its formulation is used to treat type II diabetes, overweight and / or obesity in dogs; in a preferred embodiment, the GLP-1 receptor agonist or its formulation of the present invention is used to treat obesity in dogs, wherein the canine obesity is characterized by (BCS) ≥ 6, for example, the canine obesity is characterized by (BCS) ≥ 6 and / or weight > 15 kg; preferably, the dog is over 1 year old.

[0162] 49. The method according to any one of embodiments 35-41 and 47-48, characterized in that the dosing regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.04-0.4 mg / kg QW, preferably, the dosing regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.047 mg / kg QW, 0.079 mg / kg QW, 0.4 mg / kg QW, or a combination thereof.

[0163] 50. The method according to any one of embodiments 35-41 and 47-49, characterized in that the GLP-1 receptor agonist or its formulation is administered to dogs once a week, preferably for a period of 6 weeks.

[0164] 51. The method according to any one of embodiments 35-41 and 47-50, characterized in that the dosing regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.047 mg / kg QW, 0.047 mg / kg QW, 0.079 mg / kg QW, 0.4 mg / kg QW, 0.4 mg / kg QW, or 0.4 mg / kg QW.

[0165] Terminology Definition

[0166] The "weight change rate" described in this invention is the percentage change in weight of the test substance administration group after administration, compared to before administration, reflecting the magnitude of the test substance's effect on weight. Weight change rate on day 35 (D35) = (weight...) 给药后D35 -weight 给药前 ) / weight 给药前 ×100%.

[0167] The "percentage reduction in weight" mentioned in this invention refers to the percentage reduction in weight of the test substance administration group after administration, compared to before administration, reflecting the extent of weight loss. D35 Percentage Reduction in Weight = (Weight) 给药前 -weight 给药后D35 ) / weight 给药前 ×100%.

[0168] The term "treatment" as used in this invention includes weakening, inhibiting, reversing, slowing, delaying, or stopping the progression or severity of an existing condition, disease, symptom, or illness. The term "prevention" as used in this invention includes reducing the risk of acquiring a specific disease, condition, or illness.

[0169] Unless otherwise stated or in obvious contradiction, the content of each component in the formulations of this invention, expressed in mg / mL, is based on the total volume of the formulation.

[0170] Unless otherwise stated or in obvious contradiction, the term "animal" as used in this invention refers to non-primates and non-rodents, that is, excluding humans, non-human primates, and rodents. The term "animal" as used in this invention includes pets. Unless otherwise stated or in obvious contradiction, the term "pet" as used in this invention refers to non-primate and non-rodent pets, that is, excluding primates and rodents. The term "primates" as used in this invention includes monkeys, such as cynomolgus monkeys. The term "rodents" as used in this invention includes rats and mice. Unless otherwise stated or in obvious contradiction, the terms "animal," "non-primate and non-rodent," "pet," and "non-primate and non-rodent pet" as used in this invention are used interchangeably and all include dogs, cats, rabbits, pigs, alpacas, horses, sheep, and cattle. Attached Figure Description

[0171] Figure 1 shows the weekly weight change rate of obese cats after five consecutive subcutaneous injections administered once a week (0.24, 0.24, 0.79, 0.79, 0.79 mg / kg).

[0172] Figure 2 shows the rate of change in body weight of obese cats on day 35 (D35) after five consecutive subcutaneous injections administered once weekly (0.24, 0.24, 0.79, 0.79, 0.79 mg / kg), ***p<0.001 compared with the Vehicle group.

[0173] Figure 3 shows the cumulative daily food intake of obese cats after five consecutive subcutaneous injections administered once a week (0.24, 0.24, 0.79, 0.79, 0.79 mg / kg).

[0174] Example

[0175] The reagents and raw materials are readily available to those skilled in the art. It should be understood that these embodiments are not intended to limit the scope of the invention in any way.

[0176] In vitro efficacy test: Semaglutide was provided by the laboratory, and the information is as follows: Manufacturer: MedChemExpress, Product No.: HY-114118A, Batch No.: 236924;

[0177] In vivo efficacy study: Semaglutide is the original formulation Novo Nordisk, with the following information: Manufacturer: Novo Nordisk, Batch No.: 202304BHW1, 202401BPJ1, Specification: 1.34mg / mL.

[0178] Example 1: Pharmacodynamic Test Data

[0179] 1. In vitro efficacy test methods and results

[0180] Activational activity of GLP-1 receptors in humans, cats, and dogs (LANCE Ultra cAMP assay)

[0181] 1) Agonistaltic activity against human and cat GLP-1 receptors (LANCE Ultra cAMP assay)

[0182] The GLP-1R agonist activity of the compound Semaglutide in humans and cats was determined using the LANCE Ultra cAMP Kit, with endogenous ligand GLP-1 as a reference.

[0183] CHO-K1 cells were grown at a rate of 0.6 × 10⁻⁶. 6 Cells were seeded in 6-well plates and cultured overnight at 37°C in a 5% CO2 incubator. The next day, CHO-K1 cells were changed. Two tubes (A and B) were then prepared for each plasmid. Tube A contained 100 μL of Opti-MEM, followed by 4 μL of Lipofectamine. TM Mix thoroughly. Add 100 μL of Opti-MEM to tube B, then add 2 μg of one of the plasmids (human GLP-1R-pcDNA5(+) plasmid or cat GLP-1R-pcDNA5(+) plasmid), mix well, and then add 4 μL of P3000 to tube B. TMMix thoroughly (plasmid to transfection reagent ratio: 1 μg: 2 μL). Add the diluted solution from tube A to the diluted solution from tube B, mix well, and incubate at room temperature for 15 minutes. Finally, gently add the mixture to the cells that have been given fresh medium, gently shake to mix, and then incubate overnight at 37°C with 5% CO2. Cells are used for compound functional activity assays 18-20 hours after transfection.

[0184] Human GLP-1R-CHO and feline GLP-1R-CHO cells, transfected 18-20 hours prior, were seeded at 9 μL / well in 384-well cell culture plates (2000 and 2000 cells / well, respectively) with 1×Casein Stimulation Buffer (HBSS, 5 mM HEPES, 0.5 mM IBMX, 0.1% casein, pH 7.4). 1 μL of 1×Casein Stimulation Buffer containing 10× of the compound was added to each well. The plates were incubated at 37°C for 30 minutes. After incubation, 5 μL of Eu-cAMP working solution and 5 μL of Ulight solution were added sequentially. TM -cAMP working solution, centrifuged and incubated at room temperature for 1 hour. Readings at 665nm and 620nm were detected using a microplate reader under 330nm excitation light. The 665nm / 620nm reading ratio was calculated. The response value of the highest GLP-1 concentration was set as the 100% response value. GraphPad was used to perform nonlinear regression based on the response percentage and the concentration of the added compound to obtain the EC50 of each compound. 50 value.

[0185] 2) Agonistaltic activity against canine GLP-1 receptor (LANCE Ultra cAMP assay)

[0186] The in vitro agonistic activity of the compound semaglutide against GLP-1R was determined in cells stably expressing canine GLP-1R (canine GLP-1R-HEK cells). Canine GLP-1R-HEK cells were seeded at 9 μL / well in 384-well cell culture plates (1000 cells / well) after being prepared with 1×Casein Stimulation Buffer (HBSS, 5 mM HEPES, 0.5 mM IBMX, 0.1% casein, pH 7.4). 1 μL of 1×Casein Stimulation Buffer containing 10× of the compound was added to each well. The plates were incubated at 37°C for 30 minutes. After incubation, 5 μL of Eu-cAMP working solution and 5 μL of Ulight solution were added sequentially. TM-cAMP working solution, centrifuged and incubated at room temperature for 1 hour. Readings at 665nm and 620nm were detected using a microplate reader under 330nm excitation light. The 665nm / 620nm reading ratio was calculated. The response value of the highest concentration of GLP-1 was set as the 100% response value. GraphPad was used to perform nonlinear regression based on the response percentage and the concentration of the added compound to obtain the EC50 of each compound. 50 value.

[0187] Table 1. Agonistaltic activity of GLP-1 receptors in different species, EC 50 Compare

[0188]

[0189] The agonistic activity of all compounds on the GLP-1 receptor was quantified by EC50. 50 EC 50 The smaller the value, the stronger the activity of the compound.

[0190] In summary, the compound Semaglutide exhibits good GLP-1R agonist activity in cats and dogs, indicating that cats and dogs are related species to the compound Semaglutide.

[0191] 2. In vivo efficacy test methods and results

[0192] Weight loss effect test in obese cats

[0193] This study investigated the weight-loss effect of semaglutide in obese cats by administering it subcutaneously multiple times. Cats aged 8 months and older with a Body Condition Score (BCS) ≥6 were used. Obese cats were housed in appropriately sized cages at a controlled temperature of 20–26°C and relative humidity of 40%–70%, with free access to food and water. Cats with a weight (4.8–5.1 kg) and a similar BCS (approximately 6.67) were randomly assigned to groups (n = 6 per group). Semaglutide was administered subcutaneously once weekly in escalating doses for a total of 5 weeks. The first dose of 0.24 mg / kg was given on days 1 and 8, followed by a second dose of 0.79 mg / kg on day 15, continuing until day 35.

[0194] Each animal was weighed at a fixed time every 7 days after drug administration. Feed intake was measured daily after drug administration. BCS, complete blood count, blood biochemistry, and abdominal fat volume were measured before grouping and on day 35. Body mass index (FBMI) and abdominal circumference (AC) were measured weekly. Data were statistically analyzed using t-tests with a significance level of 0.05. Both statistical and biological significance were considered in the analysis.

[0195] In the experiment conducted as described above, the BSC score of semaglutide administered 5 times is shown in Table 2. Table 2 shows that after 35 days of administration, the BSC score was 5.25±0.36*. The weight change rate is shown in Figures 1 and 2, with a weight loss of 18.54%. The cumulative food intake change is shown in Figure 3; the cumulative food intake over 35 days was only 38.35% of that in the Vehicle group (semaglutide group 708.30g, Vehicle group 1846.94g). In conclusion, semaglutide significantly reduces cumulative food intake, body weight, and BSC in obese cats, demonstrating a good weight loss effect.

[0196] Table 2. BCS Scores Note: Compared to a vehicle * p<0.05

[0197] Weight loss effect test in obese dogs

[0198] This study investigated the weight-loss effect of semaglutide in obese dogs by administering it subcutaneously multiple times. Dogs over one year old with a Body Condition Score (BCS) ≥6 were used. Obese dogs were housed in appropriately sized cages at a controlled temperature of 20–26°C and relative humidity of 40%–70%. Water was provided freely, and dogs were fed twice daily for 3 hours each time, with the first feeding between 08:30 and 11:30 and the second between 16:00 and 19:00. Dogs with a weight (~15 kg) and a similar BCS (approximately 7.2) were randomly assigned to groups (n = 6 per group). Semaglutide was administered subcutaneously once weekly, with escalating doses, for a total of 6 weeks. The first dose of 0.047 mg / kg was given on days 1 and 8, the second dose of 0.079 mg / kg was given on day 15, the second dose of 0.4 mg / kg was given on day 22, and so on until day 43.

[0199] Weight of each animal was measured at fixed times every 7 days after administration, and BCS was measured. Feed intake was measured once daily after administration. Complete blood count, blood biochemistry, and abdominal fat volume were measured before grouping and on day 42. Body mass index (BMI) and abdominal circumference (AC) of the dogs were measured weekly.

[0200] In the experiments conducted as described above, the weight change rate of the Vehicle group (D43) compared to before administration was 5.65%; after 6 doses of Semaglutide, the weight change rate of the Vehicle group (D43) compared to before administration was -1.55%, and the weight loss rate of the Semaglutide group reached 7.20% compared to the Vehicle group. This demonstrates that semaglutide reduces the weight of obese dogs and has a good weight-loss effect.

Claims

1. Use of a GLP-1 receptor agonist or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment or prevention of a disease or disease state in a pet, wherein the GLP-1 receptor agonist is semaglutide; The diseases mentioned include hyperglycemia, impaired glucose tolerance, diabetes (including type 1 and type 2 diabetes), obesity, hypertension, dyslipidemia, cognitive impairment, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular diseases, stroke, inflammatory bowel syndrome, indigestion and gastric ulcers and related complications; And / or, the compound or a pharmaceutically acceptable salt thereof is used to prepare a drug for reducing animal food intake, reducing β-cell apoptosis, increasing β-cell function and β-cell quantity and / or restoring β-cell glucose sensitivity; And / or, the diseases mentioned include metabolic disorders, dyslipidemia associated with insulin resistance and diabetes, obesity and / or hepatic steatosis; And / or, the diseases mentioned include osteopenia, bone / joint diseases such as knee osteoarthritis, hip osteoarthritis, and / or degenerative spondylitis; And / or, the compound or a pharmaceutically acceptable salt thereof may be used in overweight or obese animals as an adjunct to a low-calorie diet and increased physical activity for long-term weight management. And / or, the disease is symptomatic obesity, obesity based on simple obesity, a disease state or disease associated with obesity, eating disorder, diabetes (e.g., type 1 diabetes, type 2 diabetes, gestational diabetes, obesity-related diabetes), hyperlipidemia (e.g., hypertriglyceridemia, hypercholesterolemia, high LDL-cholesterol, low HDL-cholesterol, postprandial hyperlipidemia), hypertension, heart failure, complications of diabetes (e.g., neuropathy, nephropathy, retinopathy, diabetic cardiomyopathy, cataract, megavascular disease, osteoporosis, hyperosmolar diabetic coma), diabetic gangrene, xerostomia, hearing loss, cerebrovascular disease, peripheral circulatory disorder, metabolic syndrome (having three or more disease states selected from hypertriglyceridemia, low HDL-cholesterol, hypertension, abdominal obesity, and impaired glucose tolerance), and / or sarcopenia.

2. The use as described in claim 1, characterized in that, The symptomatic obesity includes: endocrine obesity (e.g., Cushing's syndrome, hypothyroidism, insulinoma, obesity-related type II diabetes, pseudohypoparathyroidism, hypogonadism), central obesity (e.g., hypothalamic obesity, frontal lobe syndrome, Klein-Lewin syndrome), hereditary obesity (e.g., Prader-Willi syndrome, Laureus-Muller-Bissau syndrome), and drug-induced obesity (e.g., steroid, phenothiazine, insulin, sulfonylurea drugs, beta-blocker induced obesity).

3. The use as described in claim 1, characterized in that, The disease states or conditions associated with obesity include: glucose intolerance, diabetes (especially type II diabetes, obesity-related diabetes), lipid metabolism disorders (synonymous with hyperlipidemia), hypertension, heart failure, hyperuricemia, fatty liver (including non-alcoholic hepatitis), coronary heart disease (myocardial infarction, angina pectoris), cerebral infarction (cerebral thrombosis, transient ischemic attack), bone / joint diseases (knee osteoarthritis, hip osteoarthritis, degenerative spondylitis, low back pain), sleep apnea syndrome / Pickwick syndrome, menstrual disorders (abnormal menstrual cycles, amenorrhea, abnormal menstrual symptoms), and metabolic syndrome.

4. The use as described in any one of claims 1-3, characterized in that, The GLP-1 receptor agonist is administered in formulation form.

5. The use as described in claim 4, characterized in that, The GLP-1 receptor agonist is administered in the form of a solution or suspension.

6. The use as described in claim 5, characterized in that, The formulation of the GLP-1 receptor agonist is administered via subcutaneous injection.

7. The use as described in any one of claims 5-6, characterized in that, The formulation of the GLP-1 receptor agonist preferably comprises any of the following: Option 1: Semaglutide 0.5 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide; Option 2: Semaglutide 1 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, with a pH of approximately 7.

4. The pH can be adjusted with hydrochloric acid or sodium hydroxide. Option 3: Semaglutide 2 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, with a pH of approximately 7.

4. The pH can be adjusted with hydrochloric acid or sodium hydroxide. Option 4: Semaglutide 2.27 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide; Option 5: Semaglutide 3.2 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, sodium chloride 8.25 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide; Option 6: Semaglutide 0.68 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide; Option 7: Semaglutide 1.34 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH value approximately 7.4, the pH can be adjusted with hydrochloric acid or sodium hydroxide; Option 8: Semaglutide 2.68 mg / mL, disodium hydrogen phosphate dihydrate 1.42 mg / mL, propylene glycol 1.40 mg / mL, phenol 5.50 mg / mL, and water, pH approximately 7.

4. The pH can be adjusted with hydrochloric acid or sodium hydroxide. Based on the total volume of the formulation.

8. The use as described in any one of claims 1-7, characterized in that, The pet is a dog or a cat, preferably a cat, such as a Chinese domestic cat or a blue cat, or even a Chinese domestic cat.

9. The use as described in any one of claims 1-8, characterized in that, The GLP-1 receptor agonist or its formulation is used to treat type II diabetes, overweight, and / or obesity in cats; preferably, the GLP-1 receptor agonist or its formulation is used to treat overweight and / or obesity in cats; more preferably, the overweight and / or obesity in cats is characterized by a (BCS) ≥ 6, for example, the overweight and / or obesity in cats is characterized by a (BCS) ≥ 6.6 and / or a weight > 4.5 kg, or ≥ 4.8 kg, or ≥ 4.8 kg and ≤ 5.1 kg; even more preferably, the age of the cat is 8 months or older.

10. The use as described in any one of claims 1-9, characterized in that, The dosage regimen of the GLP-1 receptor agonist or its formulation in cats is 0.2-1.6 mg / kg QW. Preferably, the dosage regimen of the GLP-1 receptor agonist or its formulation in cats is 0.24 mg / kg QW, 0.79 mg / kg QW, or a combination thereof. Preferably, the dosage regimen of the GLP-1 receptor agonist or its formulation in cats is 0.79 mg / kg QW.

11. The use as described in any one of claims 1-10, characterized in that, The GLP-1 receptor agonist or its formulation is administered to cats once a week, preferably for a period of 5 weeks.

12. The use as described in claim 11, characterized in that, The dosing regimens for the GLP-1 receptor agonist or its formulations are 0.24 mg / kg QW, 0.24 mg / kg QW, 0.79 mg / kg QW, 0.79 mg / kg QW, and 0.79 mg / kg QW.

13. The use as described in any one of claims 1-7, characterized in that, The pet is either a dog or a cat, preferably a dog.

14. The use as described in any one of claims 1-7 and 13, characterized in that, The GLP-1 receptor agonist or its formulation is used to treat type II diabetes, overweight and / or obesity in dogs; preferably, the GLP-1 receptor agonist or its formulation is used to treat overweight and / or obesity in dogs; more preferably, the overweight and / or obesity in dogs is characterized by a (BCS) ≥ 6 and / or a weight ≥ 15 kg; even more preferably, the age of the dogs is over 1 year.

15. The use as described in any one of claims 1-7 and 13-14, characterized in that, The dosage regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.04-0.4 mg / kg QW. Preferably, the dosage regimen of the GLP-1 receptor agonist or its formulation in dogs is 0.047 mg / kg QW, 0.079 mg / kg QW, 0.4 mg / kg QW, or a combination thereof.

16. The use as described in any one of claims 1-7 and 13-15, characterized in that, The GLP-1 receptor agonist or its formulation is administered to dogs once a week, preferably for a period of 6 weeks.

17. The use as described in any one of claims 1-7 and 13-16, characterized in that, The dosing regimens for the GLP-1 receptor agonist or its formulations are 0.047 mg / kg QW, 0.047 mg / kg QW, 0.079 mg / kg QW, 0.4 mg / kg QW, 0.4 mg / kg QW, and 0.4 mg / kg QW.

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